[Zinc-fans] requesting peer suggestions on docking and duplication

[John J. Irwin]

Hi Zsolt

Thanks for your email and your recent blog entry

 http://www.simbiosys.ca/blog/2008/05/17/correct-protonation-state-for-docking/#comment-1377

  about preparing a benchmarking set focusing on protonation states for 
docking. As far as I know, there is currently no good benchmarking set 
for receptor protonation, and thus this would be a welcome contribution 
to the community. As you know, the NIH recently sent out an RFA to fund 
a Drug Docking and Screening Data Resource project to assemble 
benchmarking sets for docking.

http://grants.nih.gov/grants/guide/rfa-files/RFA-GM-08-008.html

Although protonation per se was not one of the central criteria for the 
Resource, it certainly ought to figure prominently. The deadline for 
applications was March 18th 2008, reviews will be in June/July, and 
Council Review is in October.

May I suggest you lobby the successful applicant with your ideas? If for 
some reason the successful applicant were to not wish to proceed along 
the lines you propose, then I think starting up your own 
"wiki-dock-protonation-benchmark" would be very helpful.

Let me be clear: go ahead and do what you like. But perhaps you can work 
with the DDSD Resource to create something really excellent.

You asked about me personally (i.e. UCSF) getting involved. We would 
certainly be happy to host (via our wiki, or otherwise) community data 
for docking. You don't even need to ask - just create a wiki account and 
post your data. However, for deeper involvement, I perfer to wait for 
the outcome of the DDSD Resource award, which should be known, at least 
informally, in the second half of the summer of '08.

Finally, let me put in a word for the importance of prospective tests as 
well as any retrospective benchmarks. Paraphrasing Bohr, making 
predictions are particularly hard - and impressive - when they concern 
the future. I hope any benchmarking set for receptor protonation will be 
a living process that will continue to make testable predictions, and 
not just a "lookup table" based on historical precedent.

Good luck!

John
UCSF ZINC Team



Zsolt Zsoldos wrote:
> John,
>
> I know it is not exactly the profile of ZINC/DUD to work with PDB 
> complexes, but would you be interested to setting up a correctly 
> protonated complex database for cognate docking benchmarks ?
>
> Egon Willighagen has asked this on my blog in response to my detailed 
> version of the protonation post:
> http://www.simbiosys.ca/blog/2008/05/17/correct-protonation-state-for-docking/#comment-1377
>
> "Is there a gold standard; a good training set to set approaches on? 
> As you already said, crystallography is not going to help. Databases 
> with experimental pKa database are often proprietary… Any suggestions?"
>
> Since I do not know any public database with validated correct 
> protonation assignement for specific complexes, it would be a very 
> valuable thing to create. I am thinking about a community based 
> peer-reviewed project, kind of like Wikipedia, where people could 
> edit/comment/curate the data. I would be interested to help, deposit 
> PDB complexes processed by our software. But I think it would be 
> better if it is not hosted by us (commercial software vendor), I would 
> not want it to be biased, so docking.org <http://docking.org> would be 
> the perfect entity to house it.
>
> Zsolt (aka ZZ)
>
> On Sat, May 17, 2008 at 10:18 AM, John J. Irwin <jji at cgl.ucsf.edu 
> <mailto:jji at cgl.ucsf.edu>> wrote:
>
>     Hi Elite
>     >>>
>     >>> The question is, if we merge all the files into one single
>     giga SDF
>     >>> file, are the ZINC IDs unique to all the entries, meaning, can we
>     >>> safely traceback the ligand of interest to its representative pH
>     >>> subset?
>     >>>
>     You may not be able to, since we use the same ZINC ID for all
>     representations that can interconvert freely in buffer. If it is
>     important to you to know, I suggest just merging _within_ each pH
>     subset.
>
>     John
>     UCSF ZINC Team
>     _______________________________________________
>     Zinc-fans mailing list
>     Zinc-fans at docking.org <mailto:Zinc-fans at docking.org>
>     http://blur.compbio.ucsf.edu/mailman/listinfo/zinc-fans
>
>
> ------------------------------------------------------------------------
>
> _______________________________________________
> Zinc-fans mailing list
> Zinc-fans at docking.org
> http://blur.compbio.ucsf.edu/mailman/listinfo/zinc-fans
>